Studies on the interaction of safrole with rat hepatic microsomes

doi:10.1016/0006-2952(75)90367-6

Biochemical Pharmacology

Volume 24, Issue 15, 1 August 1975, Pages 1427-1433

https://doi.org/10.1016/0006-2952(75)90367-6 Get rights and content

Abstract

(1) Similar to previous results with methylenedioxyphenyl compounds microsomes from safrole pretreated rats showed, on reduction with NADH, NADPH or Na₂S₂O₄, characteristic absorption maxima at 427 and 455 nm. The same spectrum can be obtained after incubation in vitro of control microsomes with safrole, NADPH and oxygen. (2) Subsequent addition of carbon monoxide to microsomes of safrole pretreated rats causes an absorption maximum at 448 nm, characteristic of the 3-methylcholanthrene type of induction of microsomal hydroxylase protein. (3) The suspected cytochrome P-450-safrole metabolite complex, which can be visualized only in the reduced state of cytochrome P-450, is very stable as witnessed by its preservation through the preparation procedure for microsomes or after dialysis or detergent treatment. However, when safrole or ethylbenzene is added, both absorption maxima decrease in a time dependent manner. This can be measured for each time point after complete reduction of the microsomal preparation by adding Na₂S₂O₄. (4) From this it is concluded that the carcinogen safrole leads to the biosynthesis of a 3-methylcholanthrene type cytochrome P-450 and formation of a safrole metabolite-cytochrome P-450 complex which in turn can be cleaved in vitro by safrole or other lipophilic compounds.

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Studies on the interaction of safrole with rat hepatic microsomes

Abstract

Biochem. Pharmac.

Biochem. Pharmac.

Biochem. Pharmac.

Toxic. appl. Pharmac.

Biochem. Pharmac.

Biochem. Pharmac.

Biochem. Pharmac.

J. biol. Chem.

J. biol. Chem.

Archs Biochem. Biophys.

Archs Path.

Biochem. J.

Biochem. J.